Genomics in Clinical Practice, Part 1: The Rise of Multiplex Gene Testing for Cancer

Kate M. O'Rourke


July 20, 2016

In This Article

Types of Panels

Genetic tests can be evaluated based on three main criteria: analytical validity, clinical validity, and clinical utility.[7] Analytical validity is the accuracy and reproducibility of an assay to detect the presence or absence of a mutation. Clinical validity asks whether a test reliably predicts a clinically defined disorder. Clinical utility is whether a result from a test can actually improve patient outcomes.

Genes that predispose people to cancer can be divided into three different categories.[8] High-penetrance genes, such as BRCA, TP53, and PTEN, are rare variants associated with a high risk—more than 5%—of cancer. Moderate-penetrance genes, such as ATM and CHEK2, are rare genes associated with a twofold to fivefold excess risk for cancer. Low-penetrance genes, single nucleotide polymorphisms, are common and carry a low risk for cancer.

The clinical utility of multiplex gene panel testing depends on the type of panel. Several companies offer different panels that vary in scope and the number of genes included, and these panels change as new knowledge is gained (Table 1). Panels typically include high-penetrance genes, but they also often include moderate- and low-penetrance genes, and a number of genes in the panels have not been fully characterized either in terms of their cancer risk or management options.[9] In terms of cost, panels range from $249 to $6040, with most carrying a price tag of roughly $1500.[9] The turnaround time for results is 3-4 weeks.[9] "Multiplex testing is easily and inexpensively adaptable, such that you can add or remove genes as new data become available," said Dr Isaacs.

Table 1. Examples of Genes Included on Multiplex Gene Panels(a)

Panel Type of Test Genes Included
CancerNext (Ambry Genetics; Aliso Viejo, California) Comprehensive panel APC, ATM, BRCA1, BRCA2, BARD1, BRIP1, MRE11A, NBN, RAD50, RAD51C, RAD51D, BMPR1A, SMAD2, CHEK2, CDH1, CDK4, CDKN2A, GREM1, MKH1, MSH2, MSH6, PMS2, EPCAM, MUTYH, NF1, PALB2, POLD1, POLE, PTEN, SMARCA4, STK11, TP53
Breast and Gynecologic Cancers Guidelines-Based Panel (Invitae; San Francisco, California) Guideline-based panel ATM, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, PTEN, STK11, TP53/td>
COLARIS® (Myriad; Zurich, Switzerland) Site-specific panel
(a)From Lynce F, Isaacs C. Am Soc Clin Oncol Educ Book. 2016;35:e72-e78. [9]

Several categories of multiplex gene panels exist: comprehensive panels, site-specific panels, guideline-based panels, and custom panels. Comprehensive multigene panels include anywhere from 25 to 70 high- and moderate-penetrance genes for a variety of different cancers. Examples include MyRisk (Myriad), CancerNext-Expanded (Ambry Genetics; Aliso Viejo, California), and the Multi-Cancer Panel (Invitae; San Francisco, California). Site-specific panels include between 12 and 25 moderate- and high-penetrance genes associated with a particular hereditary cancer, such as breast or endometrial cancer. Some of the newest panels—guideline-based panels—focus on testing for genes for which there are clear management guidelines. Finally, there are custom panels, which allow clinicians to choose which genes they want to include in the panel for a particular patient.


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